A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity

Plain English Summary

Evaluating the Impact of Maridebart Cafraglutide on Cardiovascular Outcomes in Participants With Atherosclerotic Cardiovascular Disease and Overweight or Obesity is a Phase 3 clinical trial sponsored by Amgen studying Atherosclerotic Cardiovascular Disease, Overweight, Obesity. This trial tests a new drug called maridebart cafraglutide to see if it can lower the risk of heart attack, stroke, and death in people with existing heart disease and who are overweight or obese. It is for adults aged 45 and older who have a history of heart disease (like a past heart attack or stroke) and are overweight or obese. Participants will receive either the study drug or a placebo (a dummy treatment) by injection, in addition to their usual medical care, for up to about 35 months. Alternative treatments include standard medical care for heart disease and weight management, such as lifestyle changes and other approved medications. The trial aims to enroll 12800 participants.

Official Summary

The primary objective of this trial is to demonstrate that maridebart cafraglutide is superior to placebo when given as an adjunct to standard of care with respect to reducing cardiovascular (CV) morbidity and mortality.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 45 years or older, have a BMI of 27 or higher, and have a documented history of heart disease (like a past heart attack, stroke, or poor circulation in your legs). You cannot join if you have had a recent major heart event (within 60 days), severe heart failure, certain types of diabetes complications, or a history of pancreatitis or thyroid cancer. Specific exclusions also apply to recent use of certain diabetes or weight-loss medications, and certain liver conditions. This trial is studying Atherosclerotic Cardiovascular Disease, Overweight, Obesity, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The main goal is to see if the study drug is better than a placebo at preventing a combination of heart attack, stroke, or death from heart disease, meaning it could offer a new way to protect patient The specific primary outcome measures are: Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, Myocardial Infarction (MI), or Ischemic Stroke (3-point Major Adverse Cardiac Events [3-P MACE]) (Up to approximately 35 months); Time to First Occurrence of a Composite Endpoint Consisting of: All-cause Death, MI, Ischemic Stroke, Coronary Revascularization, or Heart Failure (HF) Event (5-point MACE) (Up to approximately 35 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial is important because it aims to find a new treatment to reduce the significant risk of major cardiovascular events in a large population with both existing heart disease and overweight or o As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Atherosclerotic Cardiovascular Disease, Overweight, Obesity, where improved treatment options are needed.

Investor Insight

This Phase 3 trial, sponsored by Amgen, targets a large patient population with atherosclerotic cardiovascular disease and obesity, a significant market. Success could lead to a new treatment option, Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 12800 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if this trial is right for you, especially considering your specific heart condition and weight. Participation involves regular clinic visits for check-ups, blood tests, and receiving study medication (either the drug or placebo) via injection. You will continue your regular medical care for heart disease and weight management alongside the trial treatment. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 12,800 participants

Interventions

• DRUG: Maridebart Cafraglutide — Maridebart cafraglutide will be administered SC.
• DRUG: Placebo — Placebo will be administered SC.

Primary Outcomes

• Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, Myocardial Infarction (MI), or Ischemic Stroke (3-point Major Adverse Cardiac Events [3-P MACE]) (Up to approximately 35 months)
• Time to First Occurrence of a Composite Endpoint Consisting of: All-cause Death, MI, Ischemic Stroke, Coronary Revascularization, or Heart Failure (HF) Event (5-point MACE) (Up to approximately 35 months)

Secondary Outcomes

• Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, MI, Ischemic Stroke, or HF Event (Up to approximately 35 months)
• Time to First Occurrence of a Composite Endpoint Consisting of: CV Death, MI, Ischemic Stroke or Coronary Revascularization (Up to approximately 35 months)
• Time to First MI (Up to approximately 35 months)
• Time to First Ischemic Stroke (Up to approximately 35 months)
• Time to CV Death (Up to approximately 35 months)

Full Eligibility Criteria

Inclusion Criteria

* Age ≥ 45 years at screening.
* BMI of ≥ 27.0 kg/m\^2 at screening.
* History of Atherosclerotic Cardiovascular Disease (ASCVD) with a documented history of at least one of the following:

  * Prior MI (presumed atherothrombotic event due to plaque rupture/erosion).
  * Prior ischemic stroke (presumed due to atherosclerosis; may include ischemic stroke with hemorrhagic transformation).
  * Symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) \< 0.9 (at rest), or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease.

Exclusion Criteria

* History of any of the following within 60 days before screening or between screening and randomization: MI, hospitalization for unstable angina, arterial revascularization (eg, coronary, cerebrovascular or peripheral) major cardiovascular surgery, stroke, or transient ischemic attack (TIA).
* New York Heart Association (NYHA) class IV HF during screening or hospitalization for HF within 60 days before screening or between screening and randomization.
* Type 1 DM, or any other type of diabetes with the exception of T2DM or prior gestational diabetes. Participants with a history of gestational diabetes should be stratified according to their current diabetes classification.
* For participants with T2DM (including those without a prior history of T2DM but with a HbA1c ≥ 6.5% during screening):

  * HbA1c \> 10.0% (86 mmol/mol) at screening.
  * History of diabetic ketoacidosis or hyperosmolar state/coma within 12 months before randomization.
  * One or more episodes of severe hypoglycemia within 6 months before randomization and/or history of hypoglycemia unawareness.
  * History of proliferative diabetic retinopathy, diabetic maculopathy, severe non-proliferative diabetic retinopathy, or currently receiving or planning to receive treatment for diabetic retinopathy and/or diabetic macular edema.
* Use of any glucagon-like peptide-1 receptor agonist (GLP-1 RA), glucose-dependent insulinotropic polypeptide (GIP) agonists or antagonists, or amylin analogs within 90 days before randomization or planned use during the conduct of the trial.
* History of chronic pancreatitis or history of acute pancreatitis in the 180 days before screening or between screening and randomization.
* Family (first-degree relative\[s\]), or personal history of medullary thyroid carcinoma (MTC), or multiple endocrine neoplasia syndrome type 2 (MEN-2).
* Calcitonin ≥ 50 ng/L (pg/mL) at screening.
* Acute or chronic hepatitis; signs and symptoms of any liver disease other than metabolic dysfunction-associated steatotic liver disease, or alanine aminotransferase (ALT) \> 3.0 x the upper limit of normal (ULN) during screening, or total bilirubin (TBL) \> 1.8 x ULN during screening (for participants with a known diagnosis of Gilbert syndrome, direct bilirubin should be used instead of TBL).
* History of malignancy within the last 5 years before screening or between screening and randomization (except for the following treated with curative intent: non-melanoma skin cancer, breast ductal carcinoma in situ, cervical carcinoma in situ, or prostate cancer in situ).
* Participants of childbearing potential planning to become pregnant while on study or unwilling to use protocol-specified methods of contraception during treatment.

Trial Locations

• Alliance For Multispecialty Research - Daphne, Daphne, Alabama, United States
• Eastern Shore Research Institute, Fairhope, Alabama, United States
• Heart Center Research LLC, Huntsville, Alabama, United States
• Mobile Heart Specialists PC, Mobile, Alabama, United States
• Syed Research Consultants LLC, Sheffield, Alabama, United States
• Synexus Clinical Research US, Inc., Phoenix, Arizona, United States
• Medical Advancement Centers of Arizona, Phoenix, Arizona, United States
• Valley Clinical Trials, LLC dba Flourish Research, Covina, California, United States
• Velocity Clinical Research- Huntington Park, Huntington Park, California, United States
• Velocity Clinical Research- Los Angeles, La Mesa, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Atherosclerotic Cardiovascular Disease
• Overweight
• Obesity
• Heart Attack (Myocardial Infarction)
• Stroke
• Peripheral Artery Disease
• Type 2 Diabetes Mellitus
• Heart Failure
• Hypertension
• Hyperlipidemia

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